UniProt functional annotation for P01139



	UniProt functional annotation for P01139

UniProt code: P01139.

Organism: Mus musculus (Mouse).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus.

Function: Nerve growth factor is important for the development and maintenance of the sympathetic and sensory nervous systems (PubMed:20036257). Extracellular ligand for the NTRK1 and NGFR receptors, activates cellular signaling cascades to regulate neuronal proliferation, differentiation and survival (PubMed:22649032). The immature NGF precursor (proNGF) functions as ligand for the heterodimeric receptor formed by SORCS2 and NGFR, and activates cellular signaling cascades that lead to inactivation of RAC1 and/or RAC2, reorganization of the actin cytoskeleton and neuronal growth cone collapse (PubMed:22155786). In contrast to mature NGF, the precursor form (proNGF) promotes neuronal apoptosis (in vitro) (PubMed:20036257). Inhibits metalloproteinase-dependent proteolysis of platelet glycoprotein VI (By similarity). Binds lysophosphatidylinositol and lysophosphatidylserine between the two chains of the homodimer (PubMed:22649032, PubMed:26144237). The lipid-bound form promotes histamine relase from mast cells, contrary to the lipid-free form (PubMed:22649032). {ECO:0000250|UniProtKB:P01138, ECO:0000269|PubMed:20036257, ECO:0000269|PubMed:22155786, ECO:0000269|PubMed:22649032, ECO:0000269|PubMed:26144237}.

Subunit: Homodimer (PubMed:1956407, PubMed:8201620, PubMed:20036257, PubMed:22649032, PubMed:26144237, PubMed:30061605). The homodimer interacts with a single NTRK1 chain (PubMed:22649032). The homodimer interacts with a single NGFR chain (By similarity). The NGF dimer interacts with a single SORCS2 chain (via extracellular domain) (PubMed:30061605). The NGF precursor (proNGF) binds to a receptor complex formed by SORT1 and NGFR, which leads to NGF endocytosis (PubMed:20036257). Both mature NGF and the immature NGF precursor (proNGF) interact with SORCS2 and with the heterodimer formed by SORCS2 and NGFR (via extracellular domains) (PubMed:22155786, PubMed:30061605). The NGF precursor (proNGF) has much higher affinity for SORCS2 than mature NGF (PubMed:24908487). The NGF precursor (proNGF) has much higher affinity for SORT1 than mature NGF (PubMed:20036257). Interacts with ADAM10 in a divalent cation-dependent manner (By similarity). {ECO:0000250|UniProtKB:P01138, ECO:0000269|PubMed:1956407, ECO:0000269|PubMed:20036257, ECO:0000269|PubMed:22155786, ECO:0000269|PubMed:22649032, ECO:0000269|PubMed:24908487, ECO:0000269|PubMed:26144237, ECO:0000269|PubMed:30061605, ECO:0000269|PubMed:8201620}.

Subcellular location: Secreted {ECO:0000269|PubMed:1284621}. Endosome lumen {ECO:0000269|PubMed:20036257}. Note=ProNGF is endocytosed after binding to the cell surface receptor formed by SORT1 and NGFR. {ECO:0000269|PubMed:20036257}.

Tissue specificity: Detected in submaxillary gland (at protein level) (PubMed:1284621). Highly expressed in male submaxillary gland. Levels are much lower in female submaxillary gland (PubMed:6336309, PubMed:1284621). {ECO:0000269|PubMed:1284621, ECO:0000269|PubMed:6336309}.

Induction: Expression oscillates in a circadian manner in the suprachiasmatic nucleus (SCN) of the brain. {ECO:0000269|PubMed:23785138}.

Similarity: Belongs to the NGF-beta family. {ECO:0000305}.

Sequence caution: Sequence=AAA37687.1; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=AAA39818.1; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=AAA39820.1; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=AAA39821.1; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=CAA24221.1; Type=Erroneous initiation; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.


Organism:		Mus musculus (Mouse).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus.



Function:		Nerve growth factor is important for the development and maintenance of the sympathetic and sensory nervous systems (PubMed:20036257). Extracellular ligand for the NTRK1 and NGFR receptors, activates cellular signaling cascades to regulate neuronal proliferation, differentiation and survival (PubMed:22649032). The immature NGF precursor (proNGF) functions as ligand for the heterodimeric receptor formed by SORCS2 and NGFR, and activates cellular signaling cascades that lead to inactivation of RAC1 and/or RAC2, reorganization of the actin cytoskeleton and neuronal growth cone collapse (PubMed:22155786). In contrast to mature NGF, the precursor form (proNGF) promotes neuronal apoptosis (in vitro) (PubMed:20036257). Inhibits metalloproteinase-dependent proteolysis of platelet glycoprotein VI (By similarity). Binds lysophosphatidylinositol and lysophosphatidylserine between the two chains of the homodimer (PubMed:22649032, PubMed:26144237). The lipid-bound form promotes histamine relase from mast cells, contrary to the lipid-free form (PubMed:22649032). {ECO:0000250\|UniProtKB:P01138, ECO:0000269\|PubMed:20036257, ECO:0000269\|PubMed:22155786, ECO:0000269\|PubMed:22649032, ECO:0000269\|PubMed:26144237}.


Subunit:		Homodimer (PubMed:1956407, PubMed:8201620, PubMed:20036257, PubMed:22649032, PubMed:26144237, PubMed:30061605). The homodimer interacts with a single NTRK1 chain (PubMed:22649032). The homodimer interacts with a single NGFR chain (By similarity). The NGF dimer interacts with a single SORCS2 chain (via extracellular domain) (PubMed:30061605). The NGF precursor (proNGF) binds to a receptor complex formed by SORT1 and NGFR, which leads to NGF endocytosis (PubMed:20036257). Both mature NGF and the immature NGF precursor (proNGF) interact with SORCS2 and with the heterodimer formed by SORCS2 and NGFR (via extracellular domains) (PubMed:22155786, PubMed:30061605). The NGF precursor (proNGF) has much higher affinity for SORCS2 than mature NGF (PubMed:24908487). The NGF precursor (proNGF) has much higher affinity for SORT1 than mature NGF (PubMed:20036257). Interacts with ADAM10 in a divalent cation-dependent manner (By similarity). {ECO:0000250\|UniProtKB:P01138, ECO:0000269\|PubMed:1956407, ECO:0000269\|PubMed:20036257, ECO:0000269\|PubMed:22155786, ECO:0000269\|PubMed:22649032, ECO:0000269\|PubMed:24908487, ECO:0000269\|PubMed:26144237, ECO:0000269\|PubMed:30061605, ECO:0000269\|PubMed:8201620}.
Subcellular location:		Secreted {ECO:0000269\|PubMed:1284621}. Endosome lumen {ECO:0000269\|PubMed:20036257}. Note=ProNGF is endocytosed after binding to the cell surface receptor formed by SORT1 and NGFR. {ECO:0000269\|PubMed:20036257}.
Tissue specificity:		Detected in submaxillary gland (at protein level) (PubMed:1284621). Highly expressed in male submaxillary gland. Levels are much lower in female submaxillary gland (PubMed:6336309, PubMed:1284621). {ECO:0000269\|PubMed:1284621, ECO:0000269\|PubMed:6336309}.
Induction:		Expression oscillates in a circadian manner in the suprachiasmatic nucleus (SCN) of the brain. {ECO:0000269\|PubMed:23785138}.
Similarity:		Belongs to the NGF-beta family. {ECO:0000305}.
Sequence caution:		Sequence=AAA37687.1; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=AAA39818.1; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=AAA39820.1; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=AAA39821.1; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=CAA24221.1; Type=Erroneous initiation; Evidence={ECO:0000305};